1. Field of the Invention
The invention relates to a microfluidic system, particularly to a microfluidic chip, with at least one operational channel in which a fluid and/or constituents contained therein are movable in the direction of the operational channel by means of a driving force, particularly by using pressure, acoustic energy, or an electrical and/or a magnetic field, and to a procedure to transport and guide a fluid and/or constituents contained therein within such a microfluidic system.
2. Description of the Related Art
Such a device and such a procedure are already known from U.S. Pat. No. 5,965,001, U.S. Pat. No. 5,800,690, and from the journal Electrophoresis (2000), pages 100 through 106 and 107 through 115. The contents of these documents are incorporated in their entirety at this point for any purpose, since these documents disclose important features, particularly regarding the design and materials formation of such microfluidic systems and concerning possible procedures for the transport and guiding of such fluids and/or the constituents contained therein within such microfluidic systems, and thus features for which individually or in combination or in combination protection is claimed in combination with the additional features disclosed in this application, for which protection is claimed.
Such microfluidic systems are of particular interest for applications in the field of electro-osmosis and/or electrophoresis, wherein the use of an open network of miniature channels, which are mutually connected by allowing fluid communication between each other, is preferred for reasons of economy and of a correspondingly expanded application spectrum. For this, the motion of the individual fluids or cells, organisms, or constituents contained therein such as particles, ions, or neutral substances, is controlled until now mainly by exertion of electrical or electro-kinetic forces, particularly by electrical voltage, electrical current, electrical power, or other electrical parameters. These electrical parameters are usually introduced into the fluid using suitable electrodes that are in contact with so-called reservoirs at each end of the partially-crossing channels, which in turn are in fluid-connection with the individual micro-channels.
Until now, a so-called method or an “assay” has been established in expensive pre-experimentation, i.e., for a given microfluidic system, preferably a microfluidic chip, certain reagents and a certain data evaluation and also a certain temporal sequence for the electrical parameters, particularly the electrical current and/or electrical voltage at specific temperatures, are compiled as a table in a so-called “script” for each electrode. The user is eventually informed of the application area of the respective microfluidic system and of its application limits in a protocol. This protocol also specifies the limits with respect to the materials or fluids to be used and their concentrations. These limits must be defined relatively narrowly also because of the time-invariable parameters, laid out statically in the script.
Corresponding to the parameters defined in the script, the electrical parameters, particularly the electrical currents and/or the electrical voltages at the individual electrodes, are altered in stages of specified time intervals during conduction of the experiment, i.e. during the practical application of the microfluidic system, wherein special electrical circuits such as current or voltage regulators ensure that the respective electrical parameters are kept constant at the respective electrode over the desired time period.
It is understood that control of the motion of the fluids and/or the constituents contained therein becomes the more difficult the more difficult the respective microfluidic system is structured, i.e., the more mutually fluid-connected micro-channels are provided. Thus, for example, in a relatively simple arrangement of four channels which are fluid-connected at one point with the formation of a cross-connection and wherein an electrode and a reservoir are provided at the ends, an independent increase in fluid flow rate between two reservoirs may be achieved not only by means of enlarging the voltage difference between two reservoirs. The voltages at the other two reservoirs must also be readjusted if the original flow rate and its direction are to be maintained. As a result, different electrical parameters are usually set at several electrodes simultaneously, i.e., according to each script. In the process the microfluidic systems are subjected to both internal and external disruptive parameter values that might strongly influence the experimental result because of the effect on any other channels present. Such disruptive parameter values may be caused, for example, by minor dimensional deviations of the microfluidic channels peculiar to their manufacture. Thus, the term “micro-fluid” pertains to miniature channels possessing a cross-section on the order of 0.1 to 500 μm. Typical dimensions of such type of miniature channels are a depth of 15 μm and a width of 40 μm, for example. The respective channel geometry determines to a great extent the effective resistance of a fluid, so that the flow rate and the electrical parameters change with an alteration of the channel geometry. Limits to the manufacturing tolerances during production of such miniature channels are however set, according to economics.
Additionally, user-specific variations caused by improper selection and preparation of fluids or substances may, for example, arise when the composition or relative salt concentration has a corresponding influence on the conductivity of the experimentation fluids and thus on the conductivity in the individual channels, which may result in a varying flow rate or migration velocity of the materials because of altered electrical parameters. Furthermore, users have shown the desire for an increased usage spectrum of such microfluidic systems, which until now could only be realized using expensive various “scripts,” if at all.
Finally, it is often of great importance during quantitative determination of materials in a separation channel that the migration velocity of the fluid and/or the constituents contained therein remain essentially constant. For this, an essentially constant voltage difference must be maintained, for a specific time period, in the designated section of the separation channel provided. This also applies, for example, to a microfluidic system in which, during the separation process, a second sample substance is “pre-positioned” or “pre-injected” up to the transition point of the supply channel that is fluid-connected to the separation channel, wherein the transition point is positioned as closely as possible to the separation channel. It is also of great importance that even the slowest component of the fluid reaches the transition point within a specified time interval, certainly before the conclusion of the separation process occurring in parallel.
In both cases, additive currents in the side channels are superposed to the driving voltage in the separation channel or pre-injection channel simultaneously with the separation process or with the pre-injection process. As a result, during use of the prescribed script for performing the tests, a false testing result may occur that is dependent on internal and external disruptive parameter values.
An additional problem during the use of electro-kinetic forces with the use of electrodes is that the electrodes cannot be directly inserted into or onto the micro-channels of the microfluidic system, since undesired gas bubbles often form on the electrodes. These gas bubbles may lead to an increase in effective resistance in the miniaturized channels up to the point where the effective resistance increases without limit. For these reasons, the electrodes are usually connected with reservoirs, which can contain a relatively large fluid volume and which obviously possess larger dimensions with respect to the geometry of the miniature channels. In this manner, use of electrodes is limited to an end of the miniature channels. The electrical parameters at the intersection points or transition points at which the individual microfluidic channels terminate to one another are frequently of interest for exact and reproducible experiments.